Cardio-Kidney Outcomes for Combined versus Monotherapy with Finerenone or SGLT2 Inhibitors in Patients with CKD

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and finerenone each improve kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD). This study compares the association between combined therapy versus monotherapy with SGLT2i or finerenone and the kidney, cardiovascular, and mortality outcomes in CKD patients. Methods This retrospective cohort study included adults ≥18 years with CKD between July 9, 2021, and November 30, 2023 from multiple centers in the United States, utilizing the TriNetX database. Exposures included treatment with finerenone, SGLT2i, or a combination of both. The primary outcome was major adverse kidney events (MAKE). Secondary outcomes included all-cause mortality, major adverse cardiac events (MACE), and end stage renal disease (ESRD). Results 853 patients were included in the combined group [mean (±SD) age, 66.7±11.4 years; 34.9% female), 942 in the finerenone group (mean age, 68.2±11.4 years; 45.8% female), and 45,948 in the SGLT2i group (mean age, 70.2±11.8 years; 41.4% female). After matching, the combined group had less MAKE compared to finerenone monotherapy [adjusted hazard ratio (aHR)=0.20; 95% CI, 0.09–0.45] or SGLT2i monotherapy (aHR=0.44; 95% CI, 0.22–0.89). The hazards of all-cause mortality and ESRD were also lower in the combined group compared to either finerenone or SGLT2i alone, while hazard of MACE was similar between the combined and monotherapy groups. The combined group had higher risk of hyperkalemia compared to SGLT2i monotherapy (aHR=1.36; 95% CI, 1.08–1.71). Conclusion Combined therapy with finerenone and SGLT2i is associated with less MAKE and all-cause mortality in CKD patients compared to monotherapy. However, the risk of hyperkalemia with finerenone warrants caution.